Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice

Schnermann J. Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice. Am J Physiol Renal Physiol 300: F339-F344, 2011. First published December 8, 2010; doi:10.1152/ajprenal.00637.2010.-Tubuloglomerular feedback (TGF), the change of afferent arteriolar resistance initiated by changes of luminal NaCl concentration, is thought to be related to NaCl-dependent release of ATP by macula densa cells. In the present study, we have explored the possibility that the released ATP may directly interact with vasoconstrictor P2 purinergic receptors in the vicinity of the glomerular vascular pole. In two different strains of wild-type mice (SWR/J and FVB), TGF responses were determined in vivo by measuring the stop flow pressure (P-SF) change caused by a saturating increase in loop of Henle flow rate before and during the administration of the P2 receptor inhibitors PPADS (12 mg/kg + 35 mg.kg(-1).h(-1) iv) or suramin (50 mg/kg + 150 mg.kg(-1).h(-1)). Both agents significantly reduced the blood pressure response to the P2X agonist alpha,beta-methylene ATP. In SWR/J and FVB mice, elevating flow to 30 nl/min reduced P-SF by 16.4 +/- 2.2 and 17.1 +/- 1.8%. During infusion of PPADS, P-SF fell by 18.8 +/- 2 (P = 0.4) and 16.5 +/- 1.5% (P = 0.82) in the two strains of mice. During suramin infusion, P-SF decreased by 14.7 +/- 2.4 (P = 0.62) and 15 +/- 1.3% (P = 0.4) in SWR/J and FVB mice, respectively. Including PPADS (10(-4) M) in the loop perfusate did not significantly alter the P-SF response (18.9 +/- 1.8%; P = 0.54). Arterial blood pressure was not systematically affected by the P2 inhibitors. As measured by free-flow micropuncture, PPADS significantly reduced proximal tubular fluid reabsorption in both fractional and absolute terms. These results indicate that the direct activation of P2 purinergic receptors by ATP is not a major cause of TGF-induced vasoconstriction in vivo.